Microsomal carboxylesterases are a family of enzymes that hydrolyse the ester and amide bonds of xenobiotics and are also thought to have a role in the metabolism of endogenous fatty acid esters. The precise function and regulation of these enzymes, however, is not well understood. In the present study, we have investigated the tissue distribution and regulation by corticosteroids of a 59 kDa form of these enzymes, which we have recently purified and characterized from rat liver microsomes. Immunoblot analysis of several tissues from rats, revealed that the enzyme is present predominantly in the liver, testes, and adipose tissue, and was decreased 3 to 6 fold in each of these tissues after treatment of rats with the corticosteroid, dexamethasone. The amount of the 59 kDa protein in the lung did not appear to be affected by treatment with dexamethasone. These findings show that the 59 kDa enzyme is present in many tissues of the body. They also indicate that corticosteroids may serve as an important pharmacological tool for elucidating the physiological function of the 59 kDa protein in each of these tissues.